Structure-function relationships during differentiation of normal and oncogene-transformed granulosa cells

Granulosa cells, which nurse the oocyte, luteinize in response to the preovulatory surge of gonadotropins and become a major producer of progesterone during the normal estrous cycle and pregnancy. This process is characterized by a dramatic change in inter- and intracellular organization and modulation of gene expression that leads to enhanced steroidogenesis. Culturing of human, porcine, and rat cells has permitted detailed studies concerning the microenvironment (hormones, growth factors, and extracellular matrices) that control steroidogenesis in a coordinated fashion both in vivo and in vitro. Reorganization of the cytoskeleton--mainly characterized by down-regulation of the actin network, which is associated with changes in cell contacts and intercellular communication--seems to be a prerequisite for up-regulation of the steroidogenic enzymes. These processes can be investigated now in more detail due to the transfection of rat granulosa cells with specific oncogenes, which leads to their immortalization, concomitantly with the preservation of their capacity for inducible steroidogenesis. The effect of oncogene expression on granulosa cell differentiation suggests that different members of the ras oncogene superfamily may be involved in controlling development and luteinization of both normal and transformed granulosa cells. The identification of the specific forms of the ras protooncogene that may be involved in the differentiation of primary granulosa cells remains a challenging objective.